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Phase I/II Study of G3139 (Genasense) in Patients With Waldenstrom's Macroglobulinemia

Phase 1/Phase 2
18 Years
Not Enrolling
Waldenström Macroglobulinemia

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Trial Information

Phase I/II Study of G3139 (Genasense) in Patients With Waldenstrom's Macroglobulinemia


I. To determine the maximally tolerated dose (MTD) and recommended dosing for Genasense in
patients with relapsed or refractory WM following prior chemotherapy. (Phase I) II. To
determine the response rate to Genasense in patients with relapsed or refractory WM
following prior chemotherapy.

III. To determine the safety of Genasense in patients with relapsed or refractory WM
following prior chemotherapy.

IV. To describe possible clinical benefit from Genasense treatment of relapsed or refractory
WM including duration of response, survival, erythropoietin use, improvement in hemoglobin >
11 g/dl, and Improvement in platelet count > 100,000/mm^3.

OUTLINE: This is a multicenter, dose-escalation study.

Phase I: Patients receive oblimersen IV continuously on days 1-7. Treatment repeats every 3
weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 1-6 patients receive escalating doses of oblimersen until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6
patients experience dose-limiting toxicity.

Phase II: Patients receive treatment as in phase I at the MTD of oblimersen. Patients are
followed every 3 months for 2 years.

Inclusion Criteria:

- Diagnosis of Waldenstrom's macroglobulinemia (WM) confirmed by both of the

- Bone marrow lymphoplasmacytosis with greater than 10% lymphoplasmacytic cells or
aggregates, sheets, lymphocytes, plasma cells, or lymphoplasmacytic cells on
bone marrow biopsy

- Measurable disease, defined by quantitative IgM monoclonal protein greater than
1,000 mg/dL

- Symptomatic relapsed or refractory disease requiring therapy, defined by at least 1
of the following:

- Impaired bone marrow function due to disease infiltration as demonstrated by
any of the following:

- Hemoglobin less than 11 g/dL

- Requires epoetin alfa therapy to maintain hemoglobin of at least 11 g/dL

- Platelet count less than 100,000/mm^3

- Symptomatic bulky lymphadenopathy

- Symptoms attributable to hyperviscosity (e.g., nose bleeding, gingival bleeding,
or retinal hemorrhage) or serum viscosity level relative to water greater than 4

- Received at least 1 prior chemotherapy regimen which included chlorambucil,
cyclophosphamide, fludarabine, cladribine, or pentostatin

- No secondary leukemia or history of antecedent hematologic disorder (e.g.,
myelodysplasia) prior to initial onset of WM

- Performance status - ECOG 0-2

- Not specified

- See Disease Characteristics

- Absolute neutrophil count at least 1,000/mm^3*

- Platelet count at least 50,000/mm^3*

- No bleeding disorder

- Bilirubin no greater than 2 times upper limit of normal (ULN)

- AST less than 1.5 times ULN

- Albumin at least 2.5 g/dL

- PT no greater than 1.5 times ULN

- INR no greater than 1.3

- PTT no greater than 1.5 times ULN

- No history of chronic hepatitis or cirrhosis

- Creatinine no greater than 2 times ULN

- No uncontrolled congestive heart failure

- No active symptoms of coronary artery disease, including the following:

- Uncontrolled arrhythmias

- Recurrent chest pain despite prophylactic medication

- No New York Heart Association class III or IV heart disease

- No grade 2 or greater cardiovascular signs and symptoms within the past 4 weeks

- HIV negative

- Direct Coombs' test negative

- No autoimmune thrombocytopenia

- No uncontrolled serious infection

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Adequate venous access for 7-day continuous infusion of study drug

- Intellectual, emotional, and physical ability to maintain an ambulatory infusion pump

- No other cancer except adequately treated basal cell or squamous cell skin cancer,
carcinoma in situ of the cervix, or other cancer from which the patient has been
disease-free for at least 5 years

- No known hypersensitivity to phosphorothioate-containing oligonucleotides

- No uncontrolled seizure disorder

- More than 21 days since prior immunotherapy for WM

- More than 21 days since prior cytokine, biologic, or vaccine therapy for WM

- More than 8 weeks since prior plasmapheresis or plasma exchange

- No prior allogeneic stem cell transplantation

- No concurrent plasmapheresis or plasma exchange

- See Disease Characteristics

- No concurrent corticosteroid therapy

- More than 21 days since prior radiotherapy for WM

- More than 21 days since prior major surgery for WM

- No prior organ allograft

- Recovered from all prior therapy

- More than 21 days since other prior therapy for WM

- No other concurrent investigational therapy

- No concurrent immunosuppressive drugs

- No concurrent therapeutic anticoagulation therapy

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose determined by the number of dose-limiting toxicity incidents graded according to CTC standard toxicity (Phase I)

Outcome Description:

Hematologic dose-limiting toxicity measures will be assessed using the continuous variables as the outcome measures (primarily nadir and percent change from baseline values) as well as categorization.

Outcome Time Frame:

21 days

Safety Issue:


Principal Investigator

Morie Gertz

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic


United States: Food and Drug Administration

Study ID:




Start Date:

May 2003

Completion Date:

Related Keywords:

  • Waldenström Macroglobulinemia
  • Waldenstrom Macroglobulinemia



Howard University Hospital Washington, District of Columbia  20060
Johns Hopkins University Baltimore, Maryland  21205
Mayo Clinic Rochester, Minnesota  55905
Barbara Ann Karmanos Cancer Institute Detroit, Michigan  48201
University of Wisconsin Hospital and Clinics Madison, Wisconsin  53792-0001
Mayo Clinic in Arizona Scottsdale, Arizona  85259-5404
Mayo Clinic in Florida Jacksonville, Florida  32224
University of Maryland Greenebaum Cancer Center Baltimore, Maryland  21201